The objectives of this study are to ascertain biological, physiological and clinical mechanisms of male reproductive disorders and to provide rational strategies of treatment for men with reproductive disease. This project represents a continuum of research begun in 1970 and includes studies of 1) the hormonal regulation of spermatogenesis in gonadotropin deficient men, 2) biology of sperm function, 3) adverse effects of cancer therapy on gonadal function, 4) evaluation of treatment of men with reproductive disorders and 5) the role of sex steroids in regulation of gonadotropin secretion. Major findings from studies performed during the past year have shown 1) that pulsatile GNRH does not improve sperm production over that achieved with exogenous gonadotropins in hypogonadotropic men, 2) that sperm of infertile men show a pattern of tail swelling after exposure to hypoosmotic medium that distinguishes it from the pattern seen in sperm of normal men, 3) that in using automated computer assisted semen analysis the quality of sperm motility in men with unexplained infertility is indistinguishable from that of normal fertile men, and 4) that estradiol, administered at physiologic dosage to castrated male rats, increases in-vitro synthesis and secretion of LH Alpha, LH Beta and free LH Alpha subunits as well as prolactin synthesis; effects opposite to those of testosterone.